David Nordsletten

University of Michigan | U-M · Department of Biomedical Engineering

Fluid-structure interaction (FSI) problems are pervasive in the computational engineering community. The need to address challenging FSI problems has led to the development of a broad range of numerical methods addressing a variety of application-specific demands. While a range of numerical and experimental benchmarks are present in the literature,...

For problems involving large deformations of thin structures, simulating fluid-structure interaction (FSI) remains challenging largely due to the need to balance computational feasibility, efficiency, and solution accuracy. Overlapping domain techniques have been introduced as a way to combine the fluid-solid mesh conformity, seen in moving-mesh me...

Many cardiovascular diseases lead to local increases in relative pressure, reflecting the higher costs of driving blood flow. The utility of this biomarker for stratifying the severity of disease has thus driven the development of methods to measure these relative pressures. While intravascular catheterisation remains the most direct measure, its i...

Characterisation of soft tissue mechanical properties is a topic of increasing interest in translational and clinical research. Magnetic resonance elastography (MRE) has been used in this context to assess the mechanical properties of tissues in vivo noninvasively. Typically, these analyses rely on linear viscoelastic wave equations to assess mater...

Assessment of tissue stiffness is desirable for clinicians and researchers, as it is well established that pathophysiological mechanisms often alter the structural properties of tissue. Magnetic resonance elastography (MRE) provides an avenue for measuring tissue stiffness and has a long history of clinical application, including staging liver fibr...

Background Decisions in the management of aortic stenosis are based on the peak pressure drop, captured by Doppler echocardiography, whereas gold standard catheterization measurements assess the net pressure drop but are limited by associated risks. The relationship between these two measurements, peak and net pressure drop, is dictated by the pres...

Atrial fibrillation (AF) underlies almost one third of all ischaemic strokes, with the left atrial appendage (LAA) identified as the primary thromboembolic source. Current stroke risk stratification approaches, such as the CHA2DS2-VASc score, rely mostly on clinical comorbidities, rather than thrombogenic mechanisms such as blood stasis, hypercoagu...

Atrial fibrillation (AF) is associated with a significantly increased risk of stroke due to the presence of three pro-thrombotic mechanisms known as Virchow’s triad – blood stasis, endothelial damage and hypercoagulability – which primarily occur in the left atrial appendage (LAA). In-silico evaluation of each factor can improve upon the current em...

Background Atrial fibrillation (AF) is responsible for almost one third of all strokes, with the left atrial appendage (LAA) being the primary thromboembolic source due to localised stimulation of prothrombotic mechanisms; blood stasis, hypercoagulability and endothelial damage, known as Virchow's triad. Aim We propose an in-silico modelling pipel...

Fluid-solid interaction (FSI) phenomena play an important role in many biomedical engineering applications. While FSI techniques and models have enabled detailed computational simulations of flow and tissue motion, the application of FSI can present challenges, particularly when data for constraining models is sparse and/or when fast computational...

Simulations of cardiac electrophysiology and mechanics have been reported to be sensitive to the microstructural anisotropy of the myocardium. Consequently, a personalized representation of cardiac microstructure is a crucial component of accurate, personalized cardiac biomechanical models. In-vivo cardiac Diffusion Tensor Imaging (cDTI) is a non-i...

Background Atrial fibrillation (AF) is responsible for almost one third of all strokes, with the left atrial appendage (LAA) being the primary thromboembolic source due to localised stimulation of prothrombotic mechanisms; blood stasis, hypercoagulability and endothelial damage, known as Virchow's triad. Aim We propose an in-silico modelling pipel...

Objective Adverse left ventricular remodeling due to a mismatch between stiffness of native aortic tissue and current polyester grafts may be under-recognized. This study was conducted to evaluate the impact of proximal aortic replacement on adverse remodeling of the left ventricle.Materials and methodsAll aortic root and ascending aortic aneurysm...

Functional mitral regurgitation (MR) in the setting of heart failure results from progressive dilatation of the left ventricle (LV) and mitral annulus. This leads to leaflet tethering with posterior displacement. Contrary to common assumptions, MR often does not resolve with LVAD decompression of the LV alone. The negative impact of significant (mo...

Pulmonary arterial hypertension (PAH) is a complex disease involving increased resistance in the pulmonary arteries and subsequent right ventricular (RV) remodeling. Ventricular-arterial interactions are fundamental to PAH pathophysiology but are rarely captured in computational models. It is important to identify metrics that capture and quantify...

Atrial fibrillation (AF) is associated with a significantly increased risk of stroke due to the presence of three pro-thrombotic mechanisms known as Virchow's triad-blood stasis, endothelial damage and hypercoagulability-which primarily occur in the left atrial appendage (LAA). In-silico evaluation of each factor can improve upon the current empiri...

Purpose Mitral regurgitation (MR) is a serious valvular pathology that impacts over 2% of the total population. Despite evidence that MR poses potentially significant risks of RV dysfunction and failure, the risks of MR are mainly assessed based on left heart parameters, including the mitral regurgitant fraction (MRF) and effective regurgitant orif...

Aortic surgeries in congenital conditions, such as hypoplastic left heart syndrome (HLHS), aim to restore and maintain the conduit and reservoir functions of the aorta. We proposed a method to assess these two functions based on 4D flow MRI, and we applied it to study the aorta in pre-Fontan HLHS. Ten pre-Fontan HLHS patients and six age-matched co...

In this paper, a time-periodic MGRIT algorithm is proposed as a means to reduce the time-to-solution of numerical algorithms by exploiting the time periodicity inherent to many applications in science and engineering. The time-periodic MGRIT algorithm is applied to a variety of linear and nonlinear single- and multiphysics problems that are periodi...

In this work we propose a new stabilized approach for solving the incompressible Navier-Stokes equations on fixed overlapping grids. This new approach is based on the partition of unity finite element method, which defines the solution fields as weighted sums of local fields, supported by the different grids. Here, the discrete weak formulation of...

The hierarchical construction of the myocardium plays a pivotal role in the biomechanics of the heart muscle and the resulting flow of blood. In disease, the construction of the heart remodels, altering the structure of the tissue from the subcellular level all the way to the whole organ. Elucidating the impact of these fundamental alterations on t...

Ventricular-vascular interaction is central in the adaptation to cardiovascular disease. However, cardiomyopathy patients are predominantly monitored using cardiac biomarkers. The aim of this study is therefore to explore aortic function in dilated cardiomyopathy (DCM). Fourteen idiopathic DCM patients and 16 controls underwent cardiac magnetic res...

Abstract Background Chronic type B aortic dissection (TBAD) is associated with poor long-term outcome, and accurate risk stratification tools remain lacking. Pressurization of the false lumen (FL) has been recognized as central in promoting aortic growth. Several surrogate imaging-based metrics have been proposed to assess FL hemodynamics; however,...

Uni-dimensional Doppler echocardiography data provide the mainstay of quantative assessment of aortic stenosis, with the transvalvular pressure drop a key indicator of haemodynamic burden. Sophisticated methods of obtaining velocity data, combined with improved computational analysis, are facilitating increasingly robust and reproducible measuremen...

In this paper, we applied a method for quantifying several left intraventricular hemodynamic parameters from 4D Flow data and its application in a proof-of-concept study in dilated cardiomyopathy (DCM) patients. In total, 12 healthy volunteers and 13 DCM patients under treatment underwent short-axis cine b-SSFP and 4D Flow MRI. Following 3D segment...

Residual stress is thought to play a critical role in modulating stress distributions in soft biological tissues and in maintaining the mechanobiological stress environment of cells. Residual stresses in arteries and other tissues are classically assessed through opening angle experiments, which demonstrate the continuous release of residual stress...

Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) allow investigations in a human cardiac model system, but disorganized mechanics and immaturity of hPSC-CMs on standard two-dimensional surfaces have been hurdles. Here, we developed a platform of micron-scale cardiac muscle bundles to control biomechanics in arrays of thousands of purif...

Atrial fibrillation (AF) is a major cause of stroke and there has been much interest in the underlying mechanisms leading to this higher risk of thrombus formation. The latter risk correlates with four morphologies of the left atrial appendage (LAA), i.e. chicken wing (CW), broccoli (BR), cactus (CA) and windsock (WS). We present a mechanistic stud...

Parameterised patient-specific models of the heart enable quantitative analysis of cardiac function as well as estimation of regional stress and intrinsic tissue stiffness. However, the development of personalised models and subsequent simulations have often required lengthy manual setup, from image labelling through to generating the finite elemen...

Elastography has become widely used clinically for characterising changes in soft tissue mechanics that are associated with altered tissue structure and composition. However, some soft tissues, such as muscle, are not isotropic as is assumed in clinical elastog-raphy implementations. This limits the ability of these methods to capture changes in an...

Objectives We examined for differences in pre-left ventricular assist device (LVAD) myocardial transcriptome between patients with different degrees of MR. Methods From 1/2018 to 10/2019, we collected left ventricular cores during durable LVAD implantation (n=72). Retrospective chart review was performed. Total RNA was isolated from LV cores and u...

The development of cerebrovascular disease is tightly coupled to changes in cerebrovascular hemodynamics, with altered flow and relative pressure indicative of the onset, development, and acute manifestation of pathology. Image-based monitoring of cerebrovascular hemodynamics is, however, complicated by the narrow and tortuous vasculature, where ac...

Understanding the biomechanics of the heart in health and disease plays an important role in the diagnosis and treatment of heart failure. The use of computational biomechanical models for therapy assessment is paving the way for personalized treatment, and relies on accurate constitutive equations mapping strain to stress. Current state-of-the art...

Purpose Hemodynamic alterations are indicative of cerebrovascular disease. However, the narrow and tortuous cerebrovasculature complicates image-based assessment, especially when quantifying relative pressure. Here, we present a systematic evaluation of image-based cerebrovascular relative pressure mapping, investigating the accuracy of the routine...

Biomechanical modeling has a wide range of applications in the medical field, including in diagnosis, treatment planning and tissue engineering. Key to these predictive models are appropriate constitutive equations that can capture the stress-strain response of materials. While most applications rely on hyperelastic formulations, experimental evide...

A major concern in personalised models of heart mechanics is the unknown zero-pressure domain, a prerequisite for accurately predicting cardiac biomechanics. As the reference configuration cannot be captured by clinical data, studies often employ in-vivo frames which are unlikely to correspond to unloaded geometries. Alternatively, zero-pressure do...

Solid tumour growth is often associated with the accumulation of mechanical stresses acting on the surrounding host tissue. Due to tissue nonlinearity, the shear modulus of the peri-tumoural region inherits a signature from the tumour expansion which depends on multiple factors, including the soft tissue constitutive behaviour and its stress/strain...

Growth and Remodelling (G&R) processes are typical responses to changes in the heart’s loading conditions. The most frequent types of growth in the left ventricle (LV) are thought to involve growth parallel to (eccentric) or perpendicular to (concentric) the fiber direction. However, hypertrophic cardiomyopathy (HCM), a genetic mutation of the sarc...

Human pluripotent stem cell derived cardiomyocytes (hPSC-CMs) allow novel investigations of human cardiac disease, but disorganized mechanics and immaturity of hPSC-CMs on two-dimensional (2D) surfaces have been hurdles for efficient and reproducible study of these cells. Here, we developed a platform of micron-scale 2D cardiac tissues (M2DCTs) to...

Understanding the biomechanics of the heart in health and disease plays an important role in the diagnosis and treatment of heart failure. The use of computational biomechanical models for therapy assessment is paving the way for personalized treatment, and relies on accurate constitutive equations mapping strain to stress. Current state-of-the art...

In this work, we describe the CRIMSON (CardiovasculaR Integrated Modelling and SimulatiON) software environment. CRIMSON provides a powerful, customizable and user-friendly system for performing three-dimensional and reduced-order computational haemodynamics studies via a pipeline which involves: 1) segmenting vascular structures from medical image...

In this paper, a time-periodic MGRIT algorithm is proposed as a means to reduce the time-to-solution of numerical algorithms by exploiting the time periodicity inherent to many applications in science and engineering. The time-periodic MGRIT algorithm is applied to a variety of linear and nonlinear single- and multiphysics problems that are periodi...

Valve annuli motion and morphology, measured from non-invasive imaging, can be used to gain a better understanding of healthy and pathological heart function. Measurements such as long-axis strain as well as peak strain rates provide markers of systolic function. Likewise, early and late-diastolic filling velocities are used as indicators of diasto...

Intracardiac blood flow is driven by differences in relative pressure, and assessing these is critical in understanding cardiac disease. Non-invasive image-based methods exist to assess relative pressure, however, the complex flow and dynamically moving fluid domain of the intracardiac space limits assessment. Recently, we proposed a method, νWERP,...

Valve annuli motion and morphology, measured from non-invasive imaging, can be used to gain a better understanding of healthy and pathological heart function. Measurements such as long-axis strain as well as peak strain rates provide markers of systolic function. Likewise, early and late-diastolic filling velocities are used as indicators of diasto...

Atrial fibrillation (AF) diminishes left atrial (LA) mechanical function and impairs blood flow. The latter can lead to blood stasis and increased risk of thrombus formation and stroke. We investigate this risk by studying the effects of LA flow in sinus rhythm (SR) and AF on blood coagulation dynamics. Patient-specific computational fluid dynamics...

In this work, we describe the CRIMSON (CardiovasculaR Integrated Modelling and SimulatiON) software environment. CRIMSON provides a powerful, customizable and user-friendly system for performing three-dimensional and reduced-order computational haemodynamics studies via a pipeline which involves: 1) segmenting vascular structures from medical image...

Soft tissue mechanical characterisation is important in many areas of medical research. Examples span from surgery training, device design and testing, sudden injury and disease diagnosis. The liver is of particular interest, as it is the most commonly injured organ in frontal and side motor vehicle crashes, and also assessed for inflammation and f...

An important number of patients with dilated cardiomyopathy have improved their left ventricular function with an optimal treatment. However, it is not well understood whether remodeling represents a recovery in left ventricular (LV) hemodynamics. In this abstract, we discuss the capacity of the ejection fraction to represent disease remission, by...

The right ventricle (RV) is often overlooked in the evaluation of cardiac performance and treatment of left ventricular (LV) heart diseases. However, recent evidence suggests the RV may play an important role in maintaining systemic cardiac function and delivering stroke volume (SV). We used exercise cardiac magnetic resonance and biomechanical mod...

Fluid-structure interaction (FSI) problems are pervasive in the computational engineering community. The need to address challenging FSI problems has led to the development of a broad range of numerical methods addressing a variety of application-specific demands. While a range of numerical and experimental benchmarks are present in the literature,...

The solid and fluid pressures of tumours are often elevated relative to surrounding tissue. This increased pressure is known to correlate with decreased treatment efficacy and potentially with tumour aggressiveness and therefore, accurate noninvasive estimates of tumour pressure would be of great value. We present a proof-of-concept method to infer...